PROJECT SUMMARY/ABSTRACT Project 4 develops nano-enabled technological solutions to environmental health challenges, and identifies mechanisms of nanotoxicity and principles of safe design in close collaboration with Agnes Kane in Project 2 as part of the Brown SRP theme of Integrated Biomedical & Engineering Solutions to Regulatory Uncertainty. Our integrated approach to nanotechnology applications and safety strives to create new environmental technologies, while ensuring their responsible development informed by data on nanomaterial hazard. We propose to fabricate and test high-performance graphene-based environmental barriers for preventing the release and transport of vapor toxicants. The impermeable, two-dimensional, space-filling geometry of graphene provides the barrier function, and its atomic-scale thickness offers the potential for ultra-low mass loadings and thus low cost. We will fabricate tiled, multilayer graphene oxide barrier films for containing mercury and trichloroethylene as model vapor toxicants. Permeability will be measured as a function of thickness, deposition method, water content, and post-processing by thermal reduction and cross-linking. We will also assess the potential to create novel graphene-based breathable barriers for personal protection that pass perspired water vapor outward while impeding the inward flow of toxicants. We will collaborate with Dr. Eric Suuberg in Project 3 to characterize the dynamic adsorption of VOCs onto these graphene-based films to understand permeation mechanisms, and will study environmental stability and degradation of graphene through long-term field studies at contaminated field sites in Rhode Island with Dr. James Rice in the RTC. Project 4 will also characterize human health risks associated with graphene inhalation in a tiered toxicity testing approach spanning Projects 2 and 4. We hypothesize that lateral dimension and surface oxidation state are the primary determinants of graphene material toxicity. In Project 4 we will create and characterize a panel of graphene materials with systematic variation in lateral dimension and surface chemistry for cellular, in vitro and in vivo testing. Project 4 will lead the acellular characterization and will characterize graphene pro-oxidant and antioxidant behaviors using electron paramagnetic resonance, dye oxidation assays, and a custom glutathione assay developed at Brown for artifact-free measurement in the presence of nanomaterials. We will also study the environmental and biological stability and degradation of graphene materials as a function of mechanical, fluid, oxidative, and radiative stressors found in biological systems and the natural environment. Finally, most nanomaterials are not used in pure form, but as formulated composites or hybrids. We will fabricate and test the cellular and biochemical behavior of copper-graphene hybrids as models for the complex exposures occurring in nanotechnology practice. This work will also assess the hypothesis that graphene encapsulation is an effective strategy for mitigating the toxicity of nanoparticles in human health applications.